Precision Neuropathology Core

The Precision Neuropathology Core-Project Summary The Precision Neuropathology (PNP) Core has been a valuable and frequently utilized resource for UW ADRC and nationally in support of its vision of characterizing and understanding heterogeneity of Alzheimer’s disease (AD) and AD-related dementias (ADRD). The PNP Core has fostered the development of enhanced methods of tissue collection and storage for use in state-of-the-art applications, including single cell molecular profiling, spatial multi-omics approaches, expanded pathological sampling informed by structural and functional imaging (network-based autopsy), ex vivo MRI-guided pathologic sampling in every brain, 3D image reconstruction, and quantitative analysis in both gross and microscopic samples, which enable us to deeply characterize the structural substrate of AD/ADRD heterogeneity. We build on this tradition of innovation by incorporating rapid cadaveric MRI on all donors, in collaboration with the Imaging and Biomarker Core, to utilize and promote characterization and image-guided sampling of optimally frozen samples that are unavailable for ex-vivo imaging. We combine comprehensive analysis of human brains with a cell types and stem cell component, providing access to and guidance on leveraging the vast resources and data available through the PNP core, including connecting researchers to experts in these fields who are committed to providing support for ADRD-related mechanistic studies. Our Aims reflect our commitment to historical continuity with integration of traditional diagnostic excellence optimized tissue preservation and characterization, functionally and radiographically informed sampling, and tissues that are application-ready for highly quantitative, molecularly specific tissue and in silico approaches to precisely measure AD/ADRD neuropathology. Our specific aims are to (i) build a highly accessible repository of brain tissue and fluid, (ii) provide diagnostic expertise according to the latest guidelines, (iii) develop innovative approaches, (iv) promote durable ADRD research through support of ADRC Cores, development projects, and local and national research (v) deploy a molecular -omics resource leveraging ongoing local brain cell atlasing efforts, (vi) promote cell types and stem cell ADRD research, and (vii) foster outreach and ADRD education. As a major point of emphasis, we leverage our infrastructure and expertise to faster development of future neuropathology core leaders. All of our research activities are focused on enhancing the research value of tissue and body fluid donations from cognitively healthy individuals and those along the ADRD spectrum in order to support every core of the ADRC and local and nation research, all while ensuring proper safeguards.